Asthma: regular beta-agonists were at greater risk of fatal or near-fatal asthma attacks.

Clinical bottom line (level 3b)

  1. Patients with asthma who used regular fenoterol or albuterol were at increased risk of having fatal or near-fatal attacks of asthma.
  2. There was a similar increase in risk for patients who required regular oral theophylline or steroids.
Spitzer et al: New England Journal of Medicine 1992; 326 (8): 501-506
Expires November 2002

The study

Case-control study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: province, Canada

784 patients (aged mean 30 years, 55% male) fatal or near-fatal asthma

Excluded if
  • <5 or >54 years old


    • Cases: 129 patients (54% male, mean age 30): long-term use of inhaled beta-agonist delivered by metered dose inhaler within 12 months of event
    Controls: 655 patients (56% male, mean age 30): matched for region of residence, receipt of social assistance, age, date of entry into study, hospitalisation at least once in the two years before the event


    Multivariate regression analysis was performed adjusting for other types of medication used, other asthma medication used and number of hospitalisations.

    Outcomes studied:
  • fatal/near-fatal asthma

    • The evidence

    Patient expected event rate for fatal/near-fatal asthma: 1.0%
    risk factor for
    fatal/near-fatal asthma     		adjusted OR
    (95% CI)    		 NNH
    (95% CI)
    fenoterol 6.10
    (3.10 to 12.2)     		21
    (10 to 49)
    albuterol 4.10
    (2.10 to 8.00)     		34
    (15 to 93)
    albuterol by nebuliser 2.50
    (1.20 to 5.50)     		68
    (23 to 510)
    theophylline 2.40
    (1.40 to 4.30)     		73
    (32 to 250)
    oral corticosteroids 2.50
    (1.50 to 4.40)     		68
    (31 to 200)

    Comments

    1. The study did not clearly adjust for the patient's severity of asthma, which is a confounding factor for use of beta-agonists.
    2. Other studies have shown no relationship between regular and intermittent beta-agonist use and severe asthma attacks in patients with mild asthma

    Citation

    1. Spitzer WO, Suissa S, Ernst P, et al: The use of ß-agonists and the risk of death and near death from asthma. New England Journal of Medicine 1992; 326 (8): 501-506
    Search Terms: acute asthma in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient asthma
    Intervention or Exposure long-term beta-agonist use
    Outcome fatal/near fatal asthma